Effect of prostaglandin E2 on urokinase-type plasminogen activator production by human lung fibroblasts.
Human lung fibroblasts are components of stromal tissue and produce various proteins as occasion demands, such as extracellular matrix (ECM) components and proteases. Pulmonary tumour cells produce high levels of prostaglandin E(2) (PGE(2)), which regulates tumour growth and metastasis. Urokinase-type plasminogen activator (uPA) is essential in the degradation of peritumour ECM. Furthermore, uPA is an important protease believed responsible for several tumour characteristics through its activation of certain proteases and growth factors. We hypothesized that the PGE(2) overexpression from tumour cells would have some effect on uPA expression in lung fibroblasts. In this study, the influence of PGE(2) on uPA expression in human lung fibroblasts was investigated using two lines of such fibroblasts. Although the cell surface uPA level was comparable to that of PGE(2) untreated cells, the expression of uPA mRNA and production was increased by the addition of PGE(2) in both lines of fibroblasts. These fibroblasts expressed both the EP(2) and EP(4) PGE(2) receptor mRNAs. Pretreatment with EP(2) and/or EP(4) receptor antagonists reduced the intercellular and cell surface uPA expression of the human lung fibroblasts. These results indicated that there is a relationship between the PGE(2) system and uPA production in human lung fibroblasts operating through EP(2) and/or EP(4) receptor signalling. uPA induced by PGE(2) from stromal fibroblasts surrounding lung tumour thus appears to play an important role through these EP receptors. Inhibition of EPs in tumour tissue might be a useful strategy for anti-metastasis therapy.
Odaka
Tomotada
T
Tokyo Medical University Kasumigaura Hospital, Fifth Department of Internal Medicine, Ami, Inashiki, Ibaraki, Japan. tomotada@i.bekkoame.ne.jp
Kobayashi
Katsuyuki
K
Takahashi
Kimiko
K
Nakamura
Hiroyuki
H
Matsuoka
Takeshi
T
D001483:Base Sequence; D001713:Biphenyl Compounds / Q000494:pharmacology; D017931:DNA Primers; D015232:Dinoprostone / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics; D044004:Xanthones / Q000494:pharmacology
D001713:Biphenyl Compounds; D017931:DNA Primers; D012333:RNA, Messenger; D044004:Xanthones; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; C046926:AH 23848; D014568:Urokinase-Type Plasminogen Activator; D015232:Dinoprostone